Campylobacter fetus ssp jejuni is a recently recognized cause of a highly prevalent form of human gastroenteritis. It is especially common in children and has a world wide distribution. There is no suitable animal model available for the study of this disease and the research proposed in this application is designed to develop one. The lower bowel of the infant mouse can be colonized for up to three weeks following intragastric infection and one strain has killed 12% of the inoculated animals. A strain recently acquired from South Africa killed 40% of 96 neonates, the most lethal of six strains tested. Other neonatal animals including guinea pigs, gerbils, rats, dogs, and chinchillas will be tested along with possibly primates (the vervet and rhesus). If necessary, immunosuppressive agents such as cyclophosphamide, hydrocortisone, and methotrexate will be used in an attempt to enhance susceptibility of the host and antibiotics will be fed so as to alter the intestinal microflora in hopes that the campylobacters will be better able to associate with the gut mucosa. The association of virulence of strains with their ability to attach to the digestive tract, produce toxin, penetrate cells, to be motile and/or induce lesions will be evaluated. In these studies, techniques for quantitating attachment, determining motility and toxinogenicity, and deciding the penetrability of the organisms into eucaryotic cells will be employed. Light and electron microscopy will be used to search for lesion formation. The immunity that develops in response to infection will be assessed by reinfection experiments, if possible. Killed cells, crude flagella and ribosomal vaccines will be used to immunize females at the time of mating or susceptible animals prior to challenge to see if passive of active immunity results. All of these immunological approaches will serve to test the variation in antigenic makeup of strains of this subspecies.